Critical Care Medicine-Infections and Immunologic Disease>>>>>Immunological Effects of Infections
Question 4#

A 23-year-old female with refractory acute lymphoblastic leukemia now 28 days postallogeneic hematopoietic stem cell transplant (HSCT) is transferred to the ICU for respiratory distress. On arrival, vital signs are:

She is saturating 88% on 10 L O2 via nonrebreather. Pulmonary examination is notable for diffuse rales. She does not have a rash, and her sclerae are mildly icteric. She is subsequently intubated and started on norepinephrine infusion for hypotension with improvement in hemodynamics. Broad-spectrum antibiotics are administered for concern of pneumonia. Chest x-ray shows diffuse bilateral patchy opacities. 

The next BEST diagnostic step is:

A. CT chest and bronchoalveolar lavage
B. Serum galactomannan, 1-3-beta-d-glucan
C. No additional workup needed, continue antibiotics
D. Herpes simplex virus (HSV) and cytomegalovirus (CMV) serum PCR

Correct Answer is A


Correct Answer: A

Pulmonary complications following HSCT are common. The differential for pulmonary complications is very broad and includes infection, diffuse alveolar hemorrhage, edema, engraftment syndrome, idiopathic pneumonia syndrome, and graft versus host disease.

Engraftment is defined as recovery of cell counts with absolute neutrophil count > 500/mm3 . Engraftment occurs within 2 to 4 weeks of transplantation. Engraftment syndrome is characterized by fever, rash, and evidence of capillary leak including pulmonary edema and weight gain. Other manifestations include dyspnea and noninfectious pulmonary infiltrates on imaging. Hepatic, renal dysfunction, or transient encephalopathy may be present. All symptoms occur within 4 days of reaching an absolute neutrophil count of 500/mm3 . Therefore, neutropenia is temporally proximal to symptoms, and empiric antibiotics should be initiated while awaiting culture data. If there is no improvement on appropriate antibiotics after 48 to 72 hours, a diagnosis of engraftment syndrome should be considered. Respiratory failure is the largest contributor to mortality related to engraftment syndrome. Treatment includes steroids (such as methylprednisolone) administered until symptoms resolve (typically 2-3 days), followed by oral prednisone. 

Patients are immunocompromised following HSCT and therefore the differential for pulmonary infections includes bacterial, fungal, and viral pathogens. Infections most commonly occur before engraftment during periods of neutropenia but may occur at any time. Viral infections in the early posttransplant period include CMV pneumonia, RSV, influenza A, B, HSV, or varicella-zoster virus (VZV). Fungal infections include aspergillus, pneumocystis and less commonly zygomycetes, rhizopus, and mucor. Treatment is initially broad-spectrum antimicrobials, which can be narrowed based on culture data.

The patient in the above vignette is 28 days post transplant. The differential is extremely broad. Therefore, workup should include bronchoalveolar lavage (BAL) to rule out diffuse alveolar hemorrhage, infectious etiologies, and CT of the chest to evaluate the presence of infection, pulmonary edema, and infiltrates. Steroids are the treatment for several of the conditions on the differential including engraftment syndrome, graft versus host disease (GVHD), and diffuse alveolar hemorrhage. However, empiric steroids without exoneration of infection would not be a correct treatment at this time. HSV and CMV PCR may diagnose viremia, however, would not exclude alternative diagnoses such as diffuse alveolar hemorrhage and GVHD and therefore are not the next best correct test. 1-3-beta-d-glucan is a fungal marker and galactomannan is elevated with invasive aspergillosis. If positive, the test suggests fungal infection. However, it would not rule out nonfungal causes of the patient’s respiratory failure.


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